[ack]pituitary adenylate cyclase activating polypeptides stimulate
duodenal bicarbonate secretion at pacap receptors in the rat.
Takeuchi, Koji, Koji Takehara, Shinichi Kato, and Koji Yagi.
Department of Pharmacology & Experimental Therapeutics, Kyoto
Pharmaceutical University, Misasagi, Yamashina, Kyoto 607, Japan
APStracts 3:0227G, 1996.
We investigated the effects of pituitary adenylate cyclase activating
polypeptides (PACAPs) on gastroduodenal HCO3- secretion in
anesthetized rats and characterized their effects by comparing with
those of vasoactive intestinal polypeptide (VIP). Under urethane
anesthesia, a rat proximal duodenal loop or a rat stomach mounted in
an ex-vivo chamber (in the absence of acid secretion) was perfused
with saline, and the HCO3- secretion was measured at pH 7.0 using a
pH-stat method and by adding 10 mM HCl. Intravenous injection of
PACAP-27 stimulated HCO3- secretion in a dose-dependent manner in the
duodenum but not in the stomach, although this peptide had no effect
on duodenal HCO3- secretion after intracisternal administration. The
duodenal HCO3- stimulatory action was similarly observed after i.v.
administration of PACAP-38 and VIP, and the potency of action was in
the following order; PACAP-27 > PACAP-38 = VIP. The duodenal
HCO3- stimulatory action of PACAP-27 was potentiated by pretreatment
with isobutylmethyl xanthine, similar to that of prostaglandin E2,
and significantly attenuated by either PACAP6-27 (PACAP antagonist),
or Ac-Tyr1, D-Phe2-VIP (VIP antagonist), but was not affected by
bilateral vagotomy or prior administra-tion of atropine, verapamil
and indomethacin. Folskolin, the stimulator of adenylate cyclase,
also increased HCO3- secretion in the duodenum but not in the
stomach. These results suggest that 1) PACAP is a potent stimulator
of HCO3- secretion in the duodenum but not in the stomach, and may be
involved in the peripheral regulation of duodenal HCO3- secretion, 2)
this action is mediated by cyclic adenosine-3'5'-monophosphate
(cAMP), probably through both PACAP- and VIP-receptors, and 3) cAMP
is a mediator in duodenal but not gastric HCO3- secretion.
Received 17 June 1996; accepted in final form 10 October 1996.0
APS Manuscript Number G245-6.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996